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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
To find the genes contributing to Down syndrome, we constructed a 4-Mb sequence-ready map spanning chromosome 21q22.2 with megabase-sized cosmid/P1-derived artificial chromosome (PAC) contigs. The restriction map with rare cutting enzymes, followed by sequencing from the clustering sites, has defined CpG islands and revealed the genes associated with CpG islands (Accession No. D85771). Of these, two human carbonyl reductases (CBR; EC1.1.1.184) were found in a PAC 25P16 clone. CBR catalyzes the reduction of a large number of biologically and pharmacologically active carbonyl compounds to their corresponding alcohols and has been mapped in 21q22. 1. To confirm these results, we sequenced the PAC clone in shotgun strategies and identified a novel carbonyl reductase, designated CBR3, 62 kb downstream from the original CBR. In addition, three ribosomal pseudogenes, L23a, S9, and L3, and some cDNAs with ESTs were mapped in the sequence. In conclusion, the sequence analysis for CpG islands predicted from the megabase-sized contigs will reveal and identify the genes involved in Down syndrome.[1]
